Possible Mechanisms Underlying the Hypertensive Response to Clonidine in Freely Moving, Normotensive Rats

• Published in: Japanese Journal of Pharmacology 1986, Vol.42(3), pp.405-417
• Main Authors: KAWASAKI, Hiromu, YAMAMOTO, Ryuichi, TAKASAKI, Koichiro
• Format: Article
• Language: English
• Subjects: Animals; Applied sciences; Biological and medical sciences; Blood Pressure - drug effects; Catecholamines - blood; Clonidine - administration & dosage; Clonidine - pharmacology; Drug Interactions; Drug toxicity and drugs side effects treatment; Exact sciences and technology; Hemodynamics - drug effects; Injections, Intravenous; Injections, Intraventricular; Male; Medical sciences; Other techniques and industries; Pharmacology. Drug treatments; Phentolamine - pharmacology; Rats; Rats, Inbred Strains; Toxicity: cardiovascular system
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.42.405

Possible mechanisms underlying the hypertensive response to intra- cerebroventricular (i.c.v.) or intravenous (i.v.) injection of clonidine were investigated in freely moving, normotensive rats. In conscious rats, clonidine (2–20 μg) injected i.c.v. caused a dose-dependent and long-lasting pressor response associated with bradycardia. A similarly long-lasting pressor response was induced following an initial rapid rise in mean blood pressure after i.v. bolus injections of clonidine (5—50 μg/kg). In pentobarbital-anesthetized rats, the prolonged pressor responses to i.v. and i.c.v. injected clonidine at high doses were significantly smaller than those in conscious rats. Low doses of clonidine caused only depressor responses which developed gradually. No significant changes in concentrations of plasma norepinephrine and epinephrine were found during the pressor period after i.c.v. injection of clonidine (20 μg). Systemic (2 mg/kg, i.v.) or central (100 μg, I.c.v.) pretreatment with phentolamine abolished only the prolonged pressor response to both I.c.v. (20 μg) and i.v. (50 μg/kg) injected clonidine. The prolonged pressor response to clonidine (20 μg, i.c.v.) was enhanced by pretreatment with hexame- thonium (25 mg/kg, i.v.), methylatropine (1 mg/kg, i.v.) or atropine (1 mg/kg, i.v.) and it was not affected by pretreatment with saralasin (300 μg/kg and 25 μg/kg/ mm, i.v.), d(CH2)BTyr(Me)-arginine-vasopressin, a vasopressin antagonist (50 μg/kg, i.v.) or naloxone (1 mg/kg, i.v.). Neither adrenalectomy nor adrenal demedullation had an effect on the pressor response to clonidine (20 μg, i.c.v.). In adrenalectomized rats, systemic pretreatment with hexamethonium (25 mg/kg, i.v.) caused a potentiation of the pressor response to clonidine (20 μg, i.c.v.). These results suggest that clonidine induces the pressor response through activation of central α-adrenoceptors, probably the α2 subtype, without an increase in sympatho-adrenomedullary activity. It is speculated that the response may be mediated by vasoactive humoral substance(s).